Amides of fatty acids (saturated and unsaturated) having the following formula: EQU R--CO--NH.sub.2
wherein the R is alkyl residue of fatty acid, represent a new group of lipid bioregulators originated from long-chain fatty acids via amidation by corresponding amines. Erucamide (13-docosenamide) was found to be the major bovine mesentery angiogenic lipid. The mechanism of angiogenic activity is unknown and this lipid does not promote proliferation of endothelial cells or induce inflammatory effects (Wakamatsu K. et al., Biochem. Biophys,. Res. Commun., V.168. p. 423-429, 1990). A molecule isolated from the cerebrospinal fluid of sleep-deprived cats has been chemically characterized and identified as cis-9,10-octadecenoamide. Other fatty acid primary amides in addition to cis-9,10-octadecenoamide were identified as natural constituents of the cerebrospinal fluid of cat, rat and human, indicating that these compounds compose a distinct family of brain lipids. Synthetic cis-9,10-octadecenoamide induced physiological sleep when injected into rats. Together, these results suggest that fatty acid primary amides may represent a previously unrecognised class of biological signal molecules (Cravatt B. F. et al., Science., V.268., P.1506-1509, 1995).
A very thoroughly investigated group of compounds are ethanol amides of fatty acids, having the following formula: EQU R--CO--NH--CH.sub.2 CH.sub.2 --OH
where R is an alkyl residue of a fatty acid.
Ethanol amides of fatty acids bound with cannabinoid receptors in the central nervous system or in peripheral tissues are considered as endogenous ligands for these receptors. They exhibit pharmacological patterns like cannabimimetics (Bezuglov V. V. et al. Biochemistry (Moscow). V.63, N 1. P. 27-37,1998).
Amides of retinoic acid (cis-trans isomers) with some amino acids having the following formula: EQU R--CO--NH--Y--COOH
wherein R is an alkyl residue of retinoic acid and Y is a residue of amino acid have been synthesised via all-trans-retinoyl chloride and an ester of the amino acid (Shealy Y. F. et al., J.Med.Chem. V.31.,P.190-196, 1988). The retinoyl derivatives of leucine, phenylalanine, alanine, tyrosine and glutamic acid were prepared. The 13-cis-retinoyl derivatives of leucine, phenylalanine, alanine, and glycine were prepared similarly from 13-cis-retinoic acid. In assays of the retynoylamino acids for reversal of squamous metaplasia in hamster trachea organ cultures, these compounds were less active than retinoic acid, but the leucine, alanine and phenylalanine derivatives were similar in activity to several retinamides that suppress bladder carcinogenesis in vivo. Two of the retinoylamino acids, as well as two simple retinamides were shown to be moderately cytotoxic to murine leukemia and human epidermoid carcinoma cells in culture.
One problem addressed by the present invention is that of making available novel compounds for use in the manufacture of pharmaceuticals, e.g. for the treatment of cancer and immune deficiencies, said compounds exhibiting i.a. higher activity than presently known compounds.